The project is aimed at further elucidating the cellular mechanisms involved in the regulation of the secretion of acid. An isolated cell system has been used because it allowed the parietal cell to be removed from the influences of its mucosal environment and separated from the other cell types. Methods have been developed for the dispersion of cells using collagenase and EDTA, for separation in various cell types using both elutriation and density gradients, and for monitoring the physiological function of the cells using oxygen uptake, morphological transformation, glucose oxidation, and the accumulation of the weak base 14C-aminopyrine. Methods have been developed for monitoring cyclic AMP generation, calcium fluxes, and for studying cell receptors using radiolabeled ligands. Histamine cells have been isolated from both canine and rat fundic mucosa using sequential velocity and density separations. Using these techniques, the following data has thus far been obtained: 1) histamine, carbachol and gastrin directly stimulate parietal cell function, 2) potentiating interactions, which may be of major importance in modulating cell function in vivo, exist between these agents, 3) using a biologically active 125I-gastrin, specific receptors have been detected on the parietal cell which appear to mediate cell response to this hormone, 4) histamine stimulation of parietal cell function is closely linked to enhanced generaton of cyclic AMP, whereas cholinergic action is closely linked to enhanced influx of calcium, 5) prostaglandins impair parietal cell function and thereby probably inhibit acid secretion by specifically interfering with histamine-stimulated generation of cyclic AMP and 6) histamine is contained in mast-like cells in the fundic mucosa of the dog but in endocrine-like cells in the fundic mucosa of the rat.